NIVO/IPI COMBO IN MELANOMA

Hodi et al found “encouraging survival outcomes” with the addition of nivolumab to ipilimumab in patients with previously untreated unresectable stage III or IV melanoma, according to 2-year overall survival data in the phase II CheckMate 069 trial. These results were reported in The Lancet Oncology.

Study Details

In the double-blind trial, 142 patients from 19 centers in the United States and France were randomized 2:1 between September 2013 and February 2014 to receive nivolumab (Opdivo) at 1 mg/kg plus ipilimumab (Yervoy) at 3 mg/kg (n = 95) vs ipilimumab at 3 mg/kg plus placebo (n = 47) every 3 weeks for 4 doses; then patients in the groups received nivolumab at 3 mg/kg vs placebo every 2 weeks until disease progression or unacceptable toxicity. A previous report on the primary endpoint of the study showed a higher objective response rate with the combination in patients with BRAF V600 wild-type melanoma. The current report is on the exploratory endpoint of overall survival.

Survival Outcomes

At median follow-up of 24.5 months, 2-year overall survival was 63.8% (95% confidence interval [CI] = 53.3%–72.6%) in the combination group vs 53.6% (95% CI = 38.1%–66.8%) in the ipilimumab group. Median overall survival was not reached in either group (hazard ratio = 0.74, P = .26).

Adverse Events

Treatment-related grade 3 or 4 adverse events were reported in 54% vs 20% of patients, with the most common being colitis (13%) and increased alanine transaminase levels (11%) in the combination group and diarrhea (11%) and hypophysitis (4%) in the ipilimumab group. Serious grade 3 or 4 treatment-related adverse events were reported in 36% vs 9%, including colitis (11%) and diarrhea (5%) in the combination group and diarrhea (4%) in the ipilimumab group. This updated analysis identified no new safety signals.

The investigators concluded: “Although follow-up of the patients in this study is ongoing, the results of this analysis suggest that the combination of first-line nivolumab plus ipilimumab might lead to improved outcomes compared with first-line ipilimumab alone in patients with advanced melanoma. The results suggest encouraging survival outcomes with immunotherapy in this population of patients.”

The study was funded by Bristol-Myers Squibb.

F. Stephen Hodi, MD, of Dana-Farber Cancer Institute, is the corresponding author of The Lancet Oncologyarticle.